NM_002458.3:c.9048G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_002458.3(MUC5B):​c.9048G>C​(p.Pro3016Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P3016P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

2 publications found
Variant links:
Genes affected
MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]
MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BP7
Synonymous conserved (PhyloP=-1.66 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC5BNM_002458.3 linkc.9048G>C p.Pro3016Pro synonymous_variant Exon 31 of 49 ENST00000529681.5 NP_002449.2 Q9HC84
MUC5B-AS1NR_157183.1 linkn.57-3290C>G intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkc.9048G>C p.Pro3016Pro synonymous_variant Exon 31 of 49 5 NM_002458.3 ENSP00000436812.1 Q9HC84
MUC5B-AS1ENST00000532061.2 linkn.57-3290C>G intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
AF:
0.00000679
AC:
1
AN:
147368
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000251
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461070
Hom.:
0
Cov.:
70
AF XY:
0.00000138
AC XY:
1
AN XY:
726834
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33456
American (AMR)
AF:
0.00
AC:
0
AN:
44694
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39678
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86228
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53284
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000450
AC:
5
AN:
1111508
Other (OTH)
AF:
0.00
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.533
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000679
AC:
1
AN:
147368
Hom.:
0
Cov.:
29
AF XY:
0.0000139
AC XY:
1
AN XY:
71710
show subpopulations
African (AFR)
AF:
0.0000251
AC:
1
AN:
39764
American (AMR)
AF:
0.00
AC:
0
AN:
14804
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3382
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4872
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4626
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10168
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
276
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
66588
Other (OTH)
AF:
0.00
AC:
0
AN:
1994
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
10
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.56
DANN
Benign
0.43
PhyloP100
-1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs139052978; hg19: chr11-1267158; API